A novel member of the Rhomboid family, RHBDD1, regulates BIK-mediated apoptosis.
Rhomboid family members are widely conserved and found in all three kingdoms of life. They are serine proteases and serve important regulatory functions. In the present study, a novel gene highly expressed in the testis, RHBDD1, is shown to be a new member of the Rhomboid family, participating in the cleavage of BIK, a proapoptotic member of the Bcl-2 family. The RHBDD1-involved proteolytic modification is upstream of the BIK protein degradation pathway. Mutagenesis studies show that the amino acid residues glycine142 and serine144 of RHBDD1 are crucial for its activity in cleaving BIK at a site located in the transmembrane region. Overexpression or knock-down of RHBDD1 in HEK 293T cells can reduce or enhance BIK-mediated apoptosis, respectively. The present findings suggest that, by acting as a serine protease, RHBDD1 modulates BIK-mediated apoptotic activity.
Wang
Y
Y
National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Tsinghua University 5 Dong Dan San Tiao, Beijing, 100005, China.
Guan
X
X
Fok
K L
KL
Li
S
S
Zhang
X
X
Miao
S
S
Zong
S
S
Koide
S S
SS
Chan
H C
HC
Wang
L
L
D017209:Apoptosis / Q000235:genetics*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D015152:Blotting, Northern; D015153:Blotting, Western; D002460:Cell Line; D017931:DNA Primers / Q000235:genetics; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D024101:Mitochondrial Proteins; D008954:Models, Biological; D016296:Mutagenesis; D034622:RNA Interference; D017422:Sequence Analysis, DNA; D012697:Serine Endopeptidases / Q000235:genetics* / Q000378:metabolism*; D013737:Testis / Q000378:metabolism*
D051017:Apoptosis Regulatory Proteins; C096820:BIK protein, human; D017931:DNA Primers; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; C534711:RHBDD1 protein, human; D012697:Serine Endopeptidases